Pharma Strategy Blog

NICE approves Tarceva in UK

In the UK, NICE has just approved Tarceva in non-small cell lung cancer (NSCLC) after Roche agreed to drop the price.

More details later.

New Avastin data in advanced breast cancer - meets primary endpoint

Genentech (DNA) has just released new data demonstrating that Avastin (bevacizumab) is effective in metastatic breast cancer:

"A Phase III study (RIBBON 1) of Avastin® (bevacizumab), in combination with taxane, anthracycline-based or capecitabine chemotherapies for first-line treatment of metastatic HER2-negative breast cancer, met its primary endpoint of increasing the time patients lived without their disease advancing, compared to the chemotherapies alone. The primary endpoint of progression-free survival (PFS) was assessed by the treating physicians in the study (investigator-assessed). The safety profile of Avastin was consistent with previous experience and no new safety signals were observed."

The trial involved 1237 women with advanced breast cancer and the findings of this study, together with the positive PFS results from the E2100 and AVADO Phase III trials support Avastin’s ability to delay cancer progression with commonly used chemotherapies in metastatic HER2-negative breast cancer.

Earlier this year the FDA conditionally approved the drug providing Roche and Genentech file additional data, defying the advice of it's advisory panel, ODAC.  However, the RIBBON 1 study should help to convert the accelerated approval granted in February to full approval.  Genentech will likely file the RIBBON 1 and AVADO data to support the full approval in 2009.  The RIBBON 1 data may make an appearance at ASCO next June.

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Excellence and success

"People at the top don't just work harder than everyone else. They work much, much harder."

"Excellence at performing a complex task requires a critical minimum of practice."

Malcolm Gladwell, Outliers

"The emerging picture from such studies is that 10,000 hours of practice is required to achieve the level of mastery associated with being a world class expert - in anything."

Daniel Levitin, Neurologist

Taxotere withdrawn from consideration by EMEA for extended indications in EU

Image via WikipediaInterestingly, it looks like French pharma company, sanofi-aventis, has decided to withdraw an application to the EU regulators to extend the indications on the cancer drug Taxotere and its generic version, Docetaxel Winthrop.

The European Medicines Agency (EMEA) announced in a press release earlier this week that it has been formally notified by sanofi-aventis that the application to use the two drugs for the adjuvant treatment of patients with operable breast cancer whose tumours overexpress HER2 has been pulled.  They were originally planned to be used in combination with Herceptin (trastuzumab) following a chemotherapy regimen based on doxorubicin and cyclophosphamide and in combination with trastuzumab and carboplatin.

Taxotere and Docetaxel Winthrop are currently indicated for the treatment of breast, non-small cell lung cancer (NSCLC) and prostate carcinoma, as well as gastric adenocarcinoma and head and neck cancer.

In July, the EMEA’s Committee for Medicinal Products for Human Use adopted a negative opinion and recommended the refusal of the extension of indication for the medicines on the grounds that the study design did not adequately define the contribution of Taxotere and Docetaxel Winthrop.  Sanofi then requested a re-examination of the opinion, which was under review by the Committee for Medicinal Products for human use (CHMP) at the time of the withdrawal.

More information will likely be available at a later date when the EMEA publishes a Q&A document on it's website.  sanofi-aventis has not yet made any formal statement on the EU withdrawal in its online press room.

FDA gets tougher on the Pharma industry via DDMAC

Image via WikipediaThe hiring of 12 new reviewers for the FDA’s Division of Drug Marketing, Advertising and Communications (DDMAC) is allowing the agency to beef up its scrutiny of Pharma promotional materials. There has been a marked increase in the number of warning and untitled letters sent to manufacturers in the past few months.

The FDA said it has a greater capacity to review promotional pieces because of staffing increases, but the agency did not say a recent spate of regulatory letters was a direct result of taking on new staff.

This move will be especially interesting for oncology, where there is significant off-label prescribing of cancer drugs by physicians based on published peer reviewed journal data.  Under the original Washington Legal Foundation FDAMA guidelines, pharma companies could give out journals describing off-label data if the physician asked for information, but many pharma companies have taken a more cautious, conservative approach in this area over the last few years as FDA became more aggressive scrutinising materials, promotional or educational.    

Source:

Drug Industry Daily

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New York Chemotherapy Meeting - some oncology notes

I have been attending the Chemotherapy Foundation symposium this week in Manhattan, an annual event held in honour of Dr Ezra Greenspan, who first created the idea.

"A non-profit organization, the Foundation supports selected laboratory and clinical research projects at major New York metropolitan medical centers, symposia for the profession, and publishes a series of free informative booklets for the profession and the public. Until his death in 2004, the pioneering oncologist Ezra M. Greenspan, M.D. was Chairman and Medical Director. Noted oncologist and investigator Franco M. Muggia, M.D. was then appointed and fulfills this leadership role." 

It's a great opportunity to catch up on snapshots of the latest data in different tumour types as well as meet and greet with pharma people and doctors alike and I try to go every year.  It's a fun meeting, with one hall for presentations, lots of variety and topics organised by session type.  It is also considerably less tiring than the large ASCO and ASH meetings where you constantly dash from Hall H to A to F to B and wear yourself out in the process.

On Wednesday, one of the interesting sessions was on GI cancers.  Jaffer Ajani reviewed modified docetaxel-based regimens in gastric cancer, including ways to optimise therapies and improve the safety profile.  Anthony El Khoueiry discussed biomarkers in colon cancer and reviewed progress to date with pathways.  The most interesting news was that the ECOG trial E5202 is looking at the potential prognostic role of 18q deletions, which may turn out to be a useful approach in the future.

Tyrosine kinase inhibitors (TKI's) were discussed by Paulo Hoff, including an overview of progress with VEGF and EGFR inhibitors plus some new ones being investigated in the clinic including Src, mTOR and others.  So far, the only targeted therapies with demonstrated effectiveness have been three monoclonal antibodies, which act extracellularly rather than intracellularly, i.e. Avastin, Erbitux and Vectibix, but in combination with chemotherapy, not each other.

Neal Meropol's presentation on circulating tumour cells as a predictive marker in colorectal cancer (CRC) highlighted the difference between predictive and prognostic markers but concluded that it is too early to tell whether this approach will be useful or not yet.  More research on phenotyping and genotyping may make it a valid approach in the future.

Sonic hedgehog signalling was the focus of Mace Rothenberg's entertaining overview.  He covered proteins, pathways, role in cancer and a quick review of the data from Genentech's compound, GDC 0449, which was licensed from Curis.  It is curently being investigated in basal cell carcinoma, ovarian cancer and CRC (in combination with Avastin).

Howard Hochster covered strategies for reducing neurotoxicity in CRC.  This occurs as  result of the duration of oxaliplatin therapy and the cumulative dose.  In trial N9741 it was shown that 63% of patients stopped the trial due to neurotoxicity rather than progressive disease.  Among the strategies suggested were optimising the oxaliplatin regimen from FOLFOX4 to FOLFOX6 and 7, adding Ca or Mg to offer neuroprotection, and consider a trial with xaliproden or xenon.  What was interesting though, is that he did ot mention another viable alternative - picoplatin, which in currently in clinical trials and may have equivalent efficacy but reduced neurotoxicity compared to oxaliplatin.  That would reduce the need to add on extra treatments and have a simple regimen for doctors to follow without fear of excessive neurotoxicity reducing the overall survival benefit.

Overall, it was a diverse and interesting meeting, definitely well worth the trip into town.

Sequencing the human genome in cancer and leukemia

Scientists at Washington University in St Louis have decoded the genes of a woman who had acute myeloid leukemia (AML) and discovered a set of mutations that may have caused the disease or aided it's progression, according to an article published today in Nature.
 
Washington University (who also provided the photo on the right of the leukemia cells), also noted in their press release:

"The researchers discovered just 10 genetic mutations in the patient's tumor DNA that appeared to be relevant to her disease; eight of the mutations were rare and occurred in genes that had never been linked to AML. They also showed that virtually every cell in the tumor sample had nine of the mutations, and that the single genetic alteration that occurred less frequently was likely the last to be acquired. The scientists suspect that all the mutations were important to the patient's cancer."

What is the significance of this fascinating research?  Well, this is the first time such sequencing has been done and may lay the foundation for more comprehensive genome-wide studies of this nature in other cancers. 

Just two of the 10 mutations the researchers found had been linked to AML previously, so the other 8 were a new and fascinating find.  They were able to do this by selecting cancer cells from the patients bone marrow and comparing them to normal, healthy skin cells.  Being able to compare the patient's normal cells to the AML cells may allows scientists to start unlocking the hidden genetic transformations and ultimately, design new therapies that target the critical mutations. 

Most work on cancer mutations has focused on a few hundred genes already suspected of being involved in the disease, not the 20,000 or so genes that make up the full human genome.  In other words, how can you hit a target if you don't know what it is?  Using this new approach, scientists can separate out which mutations are most relevant to that particular cancer patient and one day, we may be able to then determine which therapy would be most suitable for them based on the mutational analysis.

Clearly, identification of new mutations critically evolved in a cancer also means new targets for therapeutic intervention and design of new drugs based on inhibiting the specific gene or kinase, much in the way Gleevec targets the BCR-ABL gene in chronic myeloid leukemia (CML).  If a similar approach could be designed for other cancers, then it is likely that more cost effective medications with fewer side effects may result in the long run.  That's good news for patients.

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What does Obama's win mean for science and technology?

“America risks being left behind in the global economy: Revolutionary advances in information technology, biotechnology, nanotechnology and other fields are reshaping the global economy. Without renewed efforts, the United States risks losing leadership in science, technology and innovation.”

Barack Obama

So what does Obama’s election as president mean for science and technology?

Firstly, he appears to believe in openness and equality when it comes to technology. Obama and Senator Tom Coburn teamed up to pass a law that they hope will “lift the veil of secrecy in Washington”, by creating a Google-like search engine that will allow “ordinary Americans” to track federal grants, contracts, earmarks, and loans online.

While in the Senate, Obama also passed three amendments to the America COMPETES Act, which is now law, to increase participation of women and underrepresented minorities in the professions of science, technology, engineering, and mathematics.  Competitive state grants was also offered to support summer term education programs to help students develop skills in mathematics and problem solving.  The plan also wished to establish a mentoring program for women and minorities as they advance in those fields.  I'm not sure I agree with positive discrimination, but if we are to break the glass ceilings then we have to start somewhere.

Technology was also a central part of the campaign activities using computers and social networks to reach out to the younger generations and allow a dialogue to take place on Facebook, LinkedIn, Twitter and Friendfeed as well as spread the key campaign messages outside of the mainstream media.

On the science front, Obama has been a long-term supporter of increased stem cell research.  He introduced legislation while a member of the Senate that would allow embryonic stem cell research in Illinois.  He also co-sponsored legislation to allow greater federal government funding on a wider array of stem cell lines – he says he believes we need, “high ethical standards that allow for research on stem cells derived from embryos produced for in vitro fertilization, embryos that would otherwise be needlessly destroyed.”

From a cancer perspective, introducing health economic models along the lines of the UK's NICE might be bad for the pharma industry in the short term, but in the long run they will gain from any Medicare changes that limit insurance companies rejecting people because of pre-existing conditions.

The real issue at heart here is putting a basic question 'what is the right thing to do for the patient?' centre stage and going from there in a more consensus driven approach.  There is something ingerently wrong when families go into debt to pay huge medical bills for relatives who get cancer, only to find that the new therapy only added a few weeks or months of extra life at great cost.  While an overhaul of the US health system is long overdue, this may well end up a challenging and difficult task that consumes a lot of time, energy and resources. 

It will be fascinating to see how the new administration tackles this herculean task, we can but hope that change is indeed around the corner and we will all be better off for it.

“The Bush Administration has been one of the most secretive, closed administrations in American history. Our nation’s progress has been stifled by a system corrupted by millions of lobbying dollars contributed to political campaigns, the revolving door between government and industry, and privileged access to inside information - all of which have led to policies that favor the few against the public interest.”

Barack Obama

All of these ideas (and many others discussed during the long and tough campaign) are very noble and just, but with the economy badly in the tank it may take a while for these issues to get the attention they badly need.  Politics, like every thing else, is a matter of priorities and focus.

Time will tell.